Parkinson's disease (PD) is a neurodegenerative disease primarily characterized by severe motor symptoms that can be transiently relieved by medication (e.g. levodopa). These symptoms are mirrored by widespread alterations of neuronal activities across the whole brain, whose characteristics at the large scale level are still poorly understood. To address this issue, we measured the resting state activities of 11 PD patients utilizing different devices, i.e deep brain stimulation (DBS) contacts placed within the subthalamic nucleus area, and EEG electrodes placed above the motor areas. Data were recorded in each patient before drug administration (OFF-condition) and after drug administration (ON-condition). Neuronal avalanches, i.e. brief bursts of activity with widespread propagation, were detected and quantified on both types of contacts, and used to characterize differences in both conditions. Of particular interest, we noted a larger number of shorter and smaller avalanches in the OFF-condition, and a lesser number of wider and longer avalanches in the ON-condition. This difference turned out to be statistically significant at the group level. Then, we computed the avalanche transition matrices (ATM) to track the contact-wise patterns of avalanche spread. We compared the two conditions and observed a higher probability that an avalanche would spread within and between STN and motor cortex in the ON-state, with highly significant differences at the group level. Furthermore, we discovered that the increase in overall propagation of avalanches was correlated to clinical improvement after levodopa administration. Our results provide the first cross-modality assessment of aperiodic activities in PD patients, and the first account of the changes induced by levodopa on cross-regional aperiodic bursts at the individual level, and could open new avenues toward developing biomarkers of PD electrophysiological alterations.

The authors have declared no competing interest.

This study was funded by Agence Nationale de la Recherche (ANR-18-CE37-0018) SENCE and Ecole Centrale Méditerranée.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics committee/IRB of Comité de Protection des Personnes (CPP) Sud Méditerranée I gave ethical approval for this work. The registration number is RCB: 2009-A00913-54.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

The codes employed in this study are available at https://github.com/Hasnae12/neuronal_avalanches_PD. However, due to the clinical nature of the data, it can't be publicly available.